277 ‒ Food allergies: causes, prevention, and treatment with immunotherapy | Kari Nadeau, M.D., Ph.D

1. 0:00 – 0:42

   Intro

   1. KNKari Nadeau0:00

      Now luckily with therapy, there's a way to retrain your immune system, but that takes regular interaction with the food every day, not every week. If you take it every week, it actually boosts your immune system to become more allergic.

   2. PAPeter Attia0:14

      Yeah.

   3. KNKari Nadeau0:14

      Take it every day. So there's something to the circadian rhythm and the diurnal cycle, which we haven't talked about this yet, but what I love about the immune system is it can be trained and you just need to know how to train it, and you can train it away from becoming allergic and a- and train it into becoming more protective. [upbeat music]

   4. PAPeter Attia0:36

      Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Attia. [upbeat music]

2. 0:42 – 6:08

   Kari’s motivation to study food allergies

   1. PAPeter Attia0:44

      Uh, well Kari, thank you so much for, uh, for joining me today. I, I, I don't remember the last time we were together in person, but I feel like it's been probably eight years or so. Is that possible?

   2. KNKari Nadeau0:55

      I think so. It's been eight years and lots has happened, Peter, especially COVID, so it's nice to see you again.

   3. PAPeter Attia1:02

      Yeah, yeah. And I, I've always appreciated the, the amount of time you used to make for me when I used to wander into your lab at Stanford just to pick your brain. Um, and, and so again, I've always thought that the work you were doing was so exciting, and I know that it ties into so much about what people are interested in around, um, food allergies, even to some extent food sensitivities. And I think also even based on your current role, you've now left Stanford, you're at Harvard, um, I, I think it's also very interesting to discuss air pollution. Uh, I think this is, um, probably something that isn't getting enough attention with respect to health. Um, I know it's something I feel woefully deficient in my understanding, um, though I try to pay attention to my, my PM2.5s, I'm not sure what to do with the information sometimes. So w- with all that said, let's, let's maybe just give people a really quick background on, on why you're the person to be talking about this. So you, you, you're an MD PhD and, and what, what did your PhD dissertation focus on?

   4. KNKari Nadeau2:01

      Yeah, I was really excited to do my PhD in biochemistry, so I learned a lot about toxicology and biochemistry, and I did my PhD in parasitology actually. I worked on an enzyme in a parasite called the Trypanosome, which causes African sleeping sickness and another disease called Chagas disease. And I loved my work there 'cause we were able to go to the very minute levels of understanding of a chemical entity to be able to create a drug to target that entity to help people with that disease. So it was a great PhD. I loved it and I also did that at Harvard under Chris Walsh, so that's what my PhD was in, and then I did other work in immunology and, um, and animal models as well.

   5. PAPeter Attia2:45

      And then, uh, you're a pediatrician by training clinically as well. What, um, what led you then to study the, the, the field that brought me to you, uh, as, as a, as a matter of interest a decade ago around the field of food allergies?

   6. KNKari Nadeau3:02

      Yeah. You know, it's all a build, Peter, and when we think of our careers, all of these things mesh, but there are certain nexus points in our careers, and I believe that typically for me it's been a patient and it's been an inspiration to be able to move forward in a field like food allergy. So, um, I did my MD training also at Harvard and then, uh, trained in pediatrics at Children's Boston as well as at Stanford. And with that, I had the opportunity to become a fellow in a field that I loved, which was allergy, asthma, and immunology. And I had done a lot of immunology work when I did my PhD in parasites because parasites are killed by the immune cells, and especially this little molecule called IgE that tends to kill parasites, but it's not so great for allergies. So this yin and yang of this molecule in biology as an immunologist for me was also really interesting. But fast-forward, I was a fellow on the wards and I was about to see a patient that I was being asked to consult on for milk allergy. And he was in the ICU and I was told that he had just drank a cup of milk and had had a bad reaction. And by the time I arrived there, the unfortunate event of his death had already occurred. He was already being asked, um, uh, his parents were already being asked to give consent for him to be a liver donor. And so I took care of the person that was the liver recipient who also had a milk allergy. And so that really gave me pause and w- number one, inspired me and really initiated my efforts in food allergy to understand the role of this molecule called IgE, the role of the immune system, how food allergies get started in the first place, how in the world did a child with food allergy who died then give his same food allergy to the recipient of his liver? So all of these things really started to catalyze my curiosity, and I felt very blessed and lucky at the time to be able to be in a lab. And when you're a person that has this training, I feel that we're obligated in a way to be able to use that training to best help mankind and to best help those questions that parents ask us. And so at the bedside of this particular young child that had died unfortunately due to a milk allergy, I'll never forget his father trembling asking why the EpiPen didn't work at the time. What can we do to help children in the future never have to die again? And so I promised that father that I would do the absolute best to prevent further deaths in children and adults with food allergy as well as help really make sure that we educate about the use of injectable epinephrine devices and how to best use them to prevent deaths to food allergies. So that's my why, and ever since then I've always wanted to really help out in this field.

3. 6:08 – 10:37

   Overview of the immune system and the family of immunoglobulins

   1. PAPeter Attia6:08

      Kari, it, it would be impossible, I think, for us to have this discussion at the level of depth that I hope we can have it without the listener understanding how the immune system works under normal circumstances. Um, you've already alluded to one of the immunoglobulins, IgE. Um, [clears throat] does it make sense, you think, to talk about sort of the family of the immunoglobulins, what they're there for, how we acquire them, and how they normally serve us well?

   2. KNKari Nadeau6:34

      Sure. So we have certain proteins in our blood that help protect us, and that's what they're meant to do, and that's great. And they exist in different concentrations, just like in a milkshake you have different proteins that exist in different concentrations, and they're all there for nourishment purposes, um, sometimes for taste, too. But in our blood, the proteins in our blood that constitute immunoglobulins are really helpful. We learned a lot about how important immunoglobulins were to protect against COVID, for example. Everyone wanted to know their quote, unquote "titers," and what that means is immunoglobulin. So the main class, IgG immunoglobulin, those are very protective. Those are proteins that are in high amounts, and they float in our plasma. And in order to be really healthy, when we are healthy, we have healthy amounts of immunoglobulin to protect us. The minute that someone is maybe what we call under a drug like steroids or under other drugs that could affect your immune system, that also reduces the amounts of these immunoglobulins. So we know that these immunoglobulins are really important. It's important to have good concentrations, not too high, but good concentrations. And immunoglobulins in general help protect us against infections, and they also help protect us against allergies. Then there's another complementary immunoglobulin suite that doesn't just stay in our blood. It also gets into our organs, 'cause you wanna protect all of the surfaces around your organs as well, not just in your blood. The blood is great. That's the highway into so many organs. But in addition, it'd be nice to have some immunoglobulin protective molecules that actually sit around your organs and help. So for example, that class is called IgA. The other class was IgG. This class is IgA, and we call that the secretory class. And that's also helpful in our saliva, in our gut, especially, uh, women who are pregnant. They secrete it after pregnancy in their breast milk. So these are things that we've learned as immunologists that really help protect and enable health. When people are missing IgA, for example, if they don't make any IgA, they actually have allergies. And the other immunoglobulin class that I'll talk about is called IgM, and IgM is kind of a special, what I call the, the Marines. They're-- That is the type of s- immunoglobulin cell, IgM, that goes out their first call, that they're there to fight infections, but then the immunoglobulin G proteins come in afterwards, and they stay for much longer. IgMs don't stay for very long. The final class is IgE. So IgE, unfortunately, in the past, when we were in the field and, uh, fighting, uh, animals and being out there in the wild, IgE was very helpful to fight parasites, for example, and it, it was very specific to parasites. And now, unfortunately, IgE still exists in our blood. It represents .005% of all the immunoglobulins in our blood. So of all those classes, the IgE is the least represented. It's the least concentrated. But it is unfortunately the most potent, and I call it the match that lights the fire behind allergies. And you think, "Well, why do we have such a skewed response? Why do we still have this prehistoric molecule floating around in our blood that truly all of us consider a bad actor?" And we think it's because of that prehistoric need to fight parasites. Uh, but importantly now, fast-forward thousands and millions of years, it's still there, and it unfortunately has a skewed response in allergies.

4. 10:37 – 16:23

   How our immune system fights viruses, bacteria, or fungi, and some exceptions to the rule

   1. PAPeter Attia10:38

      So m- maybe just explain a little bit more about what the immunoglobulin does to fight off the... And let's just talk about it through the lens of an infection. So how-- What happens when you get a bacterial infection, um, and what happens when you get a viral infection? Those are two sort of different things, but yet they both kind of still involve immunoglobulins, even though we think of one of those threats, the viral illness, being more, uh, dealt with through the cellular immune system versus the humoral. Maybe even you can explain what cellular versus humoral immunity mean.

   2. KNKari Nadeau11:10

      Sure. So in general, what I'll explain today is how our immune system fights a virus or a bacteria or a fungi, but there's always some exceptions to the rule. But I'll just talk about the general pathway, and that, I think, helps people conceptualize what happens. And I'm always amazed at the immune system, and there's a lot we still don't know. So in all humility, as an immunologist, I learn every day what I don't know about the immune system. But what we do know is that when something attacks us, like a virus, like a bacteria, like a fungi, that enters into our lungs, our gut, our nose. Those unfortunate microbes, they know how to get into our body. So they get into our body, and they go through either the skin, or they go through other organs. And then on the other side is waiting for them a whole panoply of immune cells ready to attack And so if a virus gets in through the body, now typically it doesn't, we try to fight it right away, but sometimes it does. And so let's say a virus or a bacteria or a fungi gets into the body, gets through our typical first layer, like a skin barrier, and it gets through. Then right away we have these cells called macrophages, and they literally just eat up things. So they bind on to the virus or the bacteria or the fungi, eat it up, and then eat it up into small little bits. And then they expose those small little bits on their surface, and then with those small little bits on the surface, they actually then become the educator pieces for another group of cells called the T cell, and that's what we call the cellular system. Macrophages, antigen presenting cells, these little bits are called antigens. And then the T cell comes along and says, "Huh, that's interesting. I'm gonna teach myself the T cell. I'm gonna teach myself how to operate within these little antigens. What are these things? How do I train the immune system to get rid of this thing?" So then the T cell says, "All right, I'm gonna start to understand what this new organism is that just attacked my body, and I want to fend against that. I don't want that bacteria or that fungi or that virus in this body." So the T cell becomes what we call a memory cell. A memory T cell then teaches another cell called the B cell. The T cell interacts with the B cell. The B cell then starts to make immunoglobulins, and that B cell makes the immunoglobulins thanks for the teaching cell to train that B cell to make the immunoglobulins for the exact little antigens that that virus made or that bacteria made or that fungi made. So you have this little B cell. The B cell makes these immunoglobulins, and then they bind to the antigen. Now you have specificity in your cellular and your humoral immune system. So the humoral comes from these antibodies that float in the blood, and that's what we call the humoral immune system. It's not attached to a cell, but it was made by a cell. So those humoral related antibodies attach to the antigen, and then another cell, again, back to that macrophage eating cell, that macrophage then recognize this whole system, and we call it antibody dependent cell killing. So now that the antibody recognizes this virus and it recognizes all the viruses that maybe you had across your whole gut or across your whole lung for that one specific virus it recognizes as foreign, and then these other cells called the macrophage come back again and they chew the whole virus up and eliminate it from your body. So that's a long system. I just talked about things that take days to respond to, months to respond to, and it took many years of science to figure that whole pathway out. This is not something you learn at the bedside, uh, with some story your mom tells you. This is a lot of science, and that science has allowed us to understand the immune system to, number one, provide vaccines to people. Because of the same system, we now know how to make immunoglobulins because of our vaccines, and we know how long they can last for. These memory T cells, for example, can last up to a hundred years. So I love the cellular humoral part of the immune system because it's very instructive to fight microbes. Unfortunately, it doesn't fight all microbes. Some microbes need a little help with antibi- with antibiotics, with antivirals. So the story that I showed you today isn't perfect, so that's why you need to see the doctor. You need to have other medicines, for example, to try to help your immune system fight infections because there's holes in the immune system, and we need to help it.

5. 16:23 – 23:41

   Why our immune system is generally better at fighting viruses than bacterial infections

   1. PAPeter Attia16:23

      Why do you think our immune system is, on balance, so much better at fighting viruses than bacteria, at least in terms of the clinically relevant ones? In other words, very few people will take an antiviral drug in their life outside of, you know, a handful of unusual circumstances. Most people will go through life with their immune system doing a very good job of lopping off the head of two to three viruses a year that actually reach the threshold of clinical significance. And yet most people, you know, don't go more than two or three years without actually requiring an antibiotic to aid in the, uh, destruction of a bacteria. Do you have a sense, even teleologically, why that's the case?

   2. KNKari Nadeau17:07

      This is an excellent question teleologically as well as from an evolutionary point of view, as well as really understanding how did viruses start in the first place? How did a bacteria start in the first place? What do they need to grow? On-- From the perspective of the virus, why do they need us? From the perspective of bacteria, why do they need us? Same thing for fungi. So when you think about a virus, you know, they kind of flit from one organ to-- one organism to the other. They sometimes can exist out in the wild. They don't necessarily need us, but they do need sometimes, like HIV, it needs some of our cells to be able to live inside, to be able to keep proliferating. So I'd say in general, um, there are some viruses that are of course very severe, and they can cause fatal disease. So on the spectrum, like you said, Peter, typically though, viruses aren't as bad as bacteria. We don't typically need an antiviral because we can fight viruses. It's a great question though, because viruses can mutate in our body like we saw with COVID, and then all of a sudden we can't fight them as well. But that our body Because we make things like mucus, that we have fevers, that we have these immune cells that are really programmed to attack quickly, they can chew up the viral proteins much better and much more easily to destroy a virus 'cause a virus is really, relatively speaking compared to a bacteria, a simple organism.

   3. PAPeter Attia18:41

      It's very simple.

   4. KNKari Nadeau18:42

      It's very simple.

   5. PAPeter Attia18:43

      Yeah.

   6. KNKari Nadeau18:43

      So it doesn't take a lot for the immune system to just say, "Listen, didn't take me a lot of energy to wipe that out because that virus-

   7. PAPeter Attia18:51

      Yeah

   8. KNKari Nadeau18:51

      ... is made out of simple things. It's basically, like, made of really simple Lego blocks. But then you have the bacteria that's made of an enormous amount of Lego blocks, and it is much harder to destroy that. Same thing with fungi. They are much more complex organisms. They're made of many different materials so that it's harder for our immune system to kill every piece of the part and get rid of it. So there are certain viruses though that we still get infected with, but that they don't cause fatality, so they've learned to kind of use us and then move on because they want to just keep proliferating, but they don't necessarily stick around for our immune system to kill it. They just keep being contagious. So viruses are much easier at hopping from one person to the other, whereas bacteria, they're not s- that's not so easy because they're heavier. They're-- It's harder to take a bacteria and give it to another human. With bacteria, I also think that we have this bimodal relationship, and I want to make sure all your viewers know that there are some bacteria that are actually really good. Um, we don't know any viruses in particular that are actually good and beneficial for us, but our body h- lives with bacteria. So I think our immune system has a little tougher time to know, what is this? Is this a good bacteria or just a bad bacteria?

   9. PAPeter Attia20:13

      Hmm.

   10. KNKari Nadeau20:13

       So that's maybe also why-

   11. PAPeter Attia20:15

       That's a great point

   12. KNKari Nadeau20:15

       ... it's easier to kill viruses than bacteria. We've learned to tolerant, to be tolerant to certain bacteria, um, but not others, and some of them escape our immune system if they are bad bacteria because they know that we have this tolerance to other bacteria that are in the sim- same class. Um, but it depends on where that bacteria is. It's totally fine if this bacteria is in your gut, but the minute it gets into your blood, if it's the same bacteria, it's actually really dangerous. So that's where our immune system has to figure out, is this a bacteria in the gut? I'm okay with that. Or is this bacteria in the blood? I'm not okay with that. And bacteria tend to divide so fast, just like viruses, that for both vi- virus and bacteria, it, these, these are difficult. But when we talk about vaccines, we luckily have used science for both bacterially mediated diseases as well as viral mediated diseases. So it's really thanks to vaccines that we've enabled the immune system to get boosted for both types of infections. But it's always hard to predict mutants, to predict different infections that one would have, but I think that your question is an excellent one. I don't have all the answers.

   13. PAPeter Attia21:31

       Yeah, no, it's funny. I think there's an analogy there with cancer, right? Which is what makes cancer so challenging for the immune system is that it's basically self, and, um, it's very good at masking its non-self entities. So even though it's genetically distinct from a non-cancer cell, it's very good at hiding, uh, the neoantigens that come... You know, and sometimes they're not even coding proteins. In other words, sometimes the mutation in the cancer cell doesn't lead to the generation of an antigen, and therefore it can go completely undetected, masquerading as self.

   14. KNKari Nadeau22:07

       E- exactly, and that's the sad part about cancer, um, that our memory T cells that are supposed to be there to protect us and monitor and make sure that any cancerous cells could be killed right away, sometimes it's faked out in a way, and that's where I think the CAR T cell therapy, a lot of the T cell mediated, immune mediated therapies now can enable and better instruct our immune system, but it, that's not perfect either, so you're absolutely right, Peter. This yin and yang of having the immune system do all that it can, but w- we can't expect so much. And one of those areas in order to help our immune system, we found in COVID, for example, people that slept better, people that ate a healthy diet, people that exercised, in general, their immune system was healthier. So I think when we talk about these public health issues, and COVID kind of was the x-ray into our soul of public health and public health, uh, processes, but in that, we learned a lot about what it takes to be healthy and what it takes to have a healthy immune system to better fight viruses and, and microbes.

   15. PAPeter Attia23:17

       I'd like to actually come back to that 'cause it's such an interesting topic. It's one of those things where it seems obvious and self-evident that all of those things are true. I think I would also add stress to that. I think it's hard to, it's hard to understate the harm that hypercortisolemia and a ramped up, uh, sympathetic system to having the immune system. But I'd actually, if we have time, c- like to come back to that and, and probe a little bit about what the mechanisms

6. 23:41 – 34:38

   Differentiating a food sensitivity from a food allergy, and a discussion about celiac disease

   1. PAPeter Attia23:41

      are for that. But what I really want to get to is now pivoting to this idea of what a food allergy is. Um, and I, and I think it would pr- maybe be a good idea to differentiate between a food sensitivity and an allergy. H- I- is that the right terminology that you would use?

   2. KNKari Nadeau23:57

      Yeah, that's excellent. So for a lot of my patients, this comes up all the time, and, you know, I am inspired by how much knowledge my patients have. They come to the table, or they don't come to the table, with, um, with knowledge already that they received from the internet or podcasts such as yours and others, as well as just reading in general. And finally Asking questions is so important. If you don't know something, feel free to ask your doctor these questions. This is critical, and, um, or a healthcare provider or anyone. But I've always been really interested in this difference between food sensitivity and food allergy. So food sensitivity means that you can bite a food, and you're typically gonna react to a chemical in that food. Perhaps a protein, but it's mostly a small molecule, maybe a sugar, maybe a fat, maybe a spice. Uh, and with that, people can get headaches. People can get bloating. Uh, typical food sensitivity is, like, lactose intolerance. When you drink milk, for example, one of the sugars in the milk is called lactose, and if you don't have an enzyme in your gut and in your body called lactase, you can't break down that sugar. And so that's why people take Lactaid milk, for example. Um, and there are some ethnicities that don't have that enzyme, so there is a bunch of people that in a certain population really can't drink cow's milk because of that lactose sugar. So that's a food sensitivity. People get bloating. People get headaches. But they're not gonna have a fatal reaction. Highly unlikely.

   3. PAPeter Attia25:42

      And, and just to be clear, Kari, the immune system is not reacting at all in that state of a food sensitivity?

   4. KNKari Nadeau25:51

      Ah, great question. It can react. When you have enough lactose and you keep drinking lactose and your body says, "I don't like this sugar. Why are you keep giving me this sugar when I, when I can't break it down?" What happens is it sends its immune cells to try to break it down.

   5. PAPeter Attia26:08

      Right.

   6. KNKari Nadeau26:08

      And that causes inflammation. So some people when they take, uh, certain, uh... and preservatives as well, certain emulsifiers, these chemicals, they can get into the body, and our immune system doesn't like it 'cause the- it's foreign. A lot of our, uh, our preservatives and unfortunate emulsifiers, it hasn't been seen by the body before. It's not something that's natural. So for some people, their immune system does react. But it reacts with a different pathway than an allergic pathway. It reacts with sometimes immunoglobulins, IgGs. It reacts with something called a cytokine that isn't great because it causes chronic inflammation. So we do have some chemicals that are associated with food sensitivities that can activate the immune system in a way that's not great for the human body. And so that's why if someone does have bloating or headaches or they can still have rashes for s- food sensitivity. You can still have rashes in your skin-

   7. PAPeter Attia27:14

      Hmm

   8. KNKari Nadeau27:14

      ... with certain chemicals that you eat in foods. And if that's happening to you, then get yourself tested because we wanna make sure it's not a food allergy. But importantly is we don't have cures or therapy for food sensitivities. We often will tell people, "Please avoid that food." Like, I have someone that has terrible bloating with mushrooms because there's a certain chemical in the mushroom that bothers her immune system. Why? I don't know. But the minute she even smells the mushroom, she gets this immediate reaction to her gut that causes her to vomit, but it's not a food allergy. It's an intense reaction of the nervous system to that food chemical.

   9. PAPeter Attia27:54

      You know, sometimes we see people who have kind of a low-grade elevation of their C-reactive protein. And again, we really like to see the, the, the very sensitive version of that below one. And so you, you'll see these people that, you know, otherwise seem reasonable, but their C-reactive protein is somewhere between two and three, so it's two to three times higher than it should be, and it lingers in this state for a very long period of time. There's no- clearly no infection that's been brewing for that long. And, uh, you, you query them a little bit more, and you sort of realize that it might be attributed to food. And, and, and I would say in my experience, the two foods that far and away account for the majority of this a- as determined by simple elimination and watching this go away are first, uh, wheat-related products and secondly dairy. So, uh, again, m- when I say wheat, I don't mean celiac disease, which I'd like you to explain as a contrast, but, but rather some sort of low-grade sensitivity. And so what you're saying is there's nothing going on in the IgE pathway, but there is something going on in the IgG pathway. And again, C-reactive protein is made by the liver as basically a calling sign to the immune system. So you're, you're sort of seeing, for lack of a better word, you're seeing the sirens going constantly, which is CRP.

   10. KNKari Nadeau29:17

       Yeah. It's a great, great analogy, and, and Peter, it's a excellent question because we can measure what we can measure. And CRP's been around in our sort of doctor's handbag for a while, and it's actually a really good beacon like you analog- analogized because it does tell us something's going on there, and it is kind of, um, a, a window into what's going on chronically in the immune system. So yes, when I test the CRP levels in my patients with food sensitivities and they're not able to eliminate that specific chemical, then I see the CRP kind of in, in that kind of range where it's a s- I call it simmering immune inflammation. It's not a fire, but it's simmering. And the problem with food sensitivities is I don't have a great way to diagnose them. I don't have a skin test. I don't have an-

   11. PAPeter Attia30:09

       Mm-hmm

   12. KNKari Nadeau30:09

       ... IgE test. I have to do elimination, and then I follow that CRP level until it can try to get to zero. But that's not easy because some of these chemicals are so systematically in our food supply that it's hard to get rid of. So that's food Sensitivity. And I agree with you, milk and wheat are some of the most associated culprits in food sensitivities, especially in the US, and that might be for a lot of different reasons in terms of how we process and how we have detergents in our milk, and the same thing with our wheat products. It isn't necessarily the same wheat that we ate when we were, uh, when our ancestors-

   13. PAPeter Attia30:45

       Yeah

   14. KNKari Nadeau30:45

       ... ate it originally. So maybe there's a lot of reasons for that. But let me bring it to wheat because, uh, this triangulation of food sensitivity, celiac versus food allergy, and we'll get to food allergy. But let me just transpose this interesting comment you made about food sensitivity versus celiac. So celiac is a very specific type of food sensitivity, and it has a very marched out pathway of immune reaction to that wheat, and that wheat protein and specifically is the gliadin, which is a part of the wheat. And celiac disease also has genetics associated with it and other autoimmune disease with it, as you know. But that reaction is to a very specific part of the protein of the wheat, and not everyone with a food sensitivity to wheat has celiac, and certainly not everyone with celiac will have the same type of reactions to wheat as the food sensitivity people do. Now, celiac we take extremely seriously because it can result in long-term problems with your gut. And so it has its own special category. But you shouldn't call yourself someone that has celiac just because you have a food sensitivity to wheat. There's a specific diagnosis that needs to occur with a professional that specializes in gastroenterology or in celiac to be able to know if I truly have celiac disease. And if you do, then it's important to test family members and to really get under the care of a good doctor. And I hope that that's helpful to differentiate food sensitivity to celiac.

   15. PAPeter Attia32:27

       Yeah.

   16. KNKari Nadeau32:27

       Are there any other questions you have on that?

   17. PAPeter Attia32:30

       No. I mean, I, I was gonna ask you, you know, are, are we seeing any increase in the prevalence of celiac disease, or are we seeing any increase in the prevalence of food sensitivities? It certainly seems like it, as a non-epidemiologist who pays attention only to the world around him. But it seems like more and more people are saying, uh, "Boy, I'm really struggling to eat," fill in the blank.

   18. KNKari Nadeau32:57

       Yeah. On one side I think that people are becoming more knowledgeable about this, and they also feel they have agency, as they should, when they come to the doctor to be able to say, "I think I have a sensitivity to this food." And, and people take them seriously, and that's good, and we need that because these symptoms are serious. They're affecting someone's quality of life. We need to help. And in the past maybe they were kind of pooh-poohed and said, "Oh, I can't help you, so I can't do anything about that." But now people like you and I can say, "Well, let's test that CRP. Let's see if we can d- be better detectives and really try to help you." Because in the end we wanna help quality of life. So yes, people I think are feeling more and more like they can talk about it, as well as celiac disease, but importantly is we have better diagnostics. So I think that we as a community have gotten better at really, uh, diagnosing celiac, so I think that's another good reason why there might be more people with it. I think people also are seeing an increase in food sensitivities and celiac because of the different ways that wheat is processed, uh, because of the different detergents now and unfortunate chemicals that are put into our foods. So I think we have to be careful about that, and hopefully the food industry and agriculture will think carefully about those chemicals before they put them in because I've seen an increase. And when I tell people to not eat foods with those chemicals in them, they tend to not have food sensitivities. So I, I think that perhaps, and I would be interested in your comment too, Peter, that might be one of the reasons why there's more food sensitivity, although I don't... I can't put my finger on it.

7. 34:38 – 50:11

   How food allergies develop, why they can be lethal, and factors contributing to the uptrend in food allergies

   1. PAPeter Attia34:39

      Yeah. It's, it... I, I feel like there's something going on and, and I know we're gonna talk about this also on the food allergy side, where I think we can probably speak with more clarity. So, so let's now, let's now talk about that because I think this is the area where, you know... I... Let's just start with some statistics. Uh, do you have a sense of how many people in the United States die in a year as a result of a food allergy, like the tragic story you told?

   2. KNKari Nadeau35:05

      Yeah. Thankfully, it is extremely rare. Um, the reason why I hedge is because nowadays with the codes in the emergency rooms and understanding if someone died from a food allergy, some emergency rooms, some intensive care units, they're able to ascribe or attribute a certain reaction exactly to a food. Sometimes it's a little blurry. So it is very rare. There are people around the country, in Michigan as well as in Chicago, that are epidemiologists. I am not an epidemiologist, although I love to work with epidemiologists. So it is very rare. Um, people have claimed that, um, it's... One of the reasons why people can have a fatal attack is because they don't have access to an Epi, uh, device, or they don't have anticipatory guidance for what to do during a reaction. So any, in my mind, any fatal reaction could have been avoided.

   3. PAPeter Attia36:01

      Yeah.

   4. KNKari Nadeau36:01

      And that's what I learned from that case, is even though the fatal reactions are rare, and that's good, um, they can be avoided. And when we learn about them, and I learn about one per month, right, in, in the US, and it's very sad. Every one of those stories comes with, um, a tragedy that's heart-wrenching. But it compels me to keep training my patients on making sure they have two injectable epinephrine devices at all times, making sure they know how to use it within a minute, making sure that if it doesn't help their symptoms within a minute that they use another right away, that it's okay to use an injectable epinephrine device because that's the only thing that can actually prevent The unfortunate death. And so I think the numbers right now in terms of death rates are getting lower, which is good because people are understanding more about this disease, and the communities understand that why we don't wanna expose people unnecessarily to foods that could kill them. But in addition, there are increasing incidence and prevalence of food allergies in general in the US. So for example, my colleague Ruchi Gupta out of Chicago, she published data that 1 in every 12 children in the classroom in the US has a doctor's diagnosis of food allergy. And we used to think that children would lose their food allergy, especially those with milk and egg. So it used to be thought, even when I was training, that children with milk and egg allergies, if they were under the age of five, there was like an 80% chance that they would lose these allergies by the time they were teenagers. But if it was peanut or, or any kind of tree nut or shrimp or fish, they had an 80% chance of keeping it. But now, unfortunately, if you have a milk or an egg allergy and you're under the age of five, you have a 50% chance of losing it. So now we see more and more adults having food allergy. And the other unfortunate thing, Peter, is that more adults when they get to adulthood are getting food allergies. And so that's presumably about 1 in 30 adults will have some type of food allergy when they're an adult, whether or not that's because they had it when they were children or because they gain it newly when they're an adult. So the numbers are rising. Luckily, the death numbers are not, but someone needs to do more research on that. But this compels me as a food allergist to really make sure that both children and adults understand this disease and how to manage it.

   5. PAPeter Attia38:44

      So let's talk about how this occurs. And let's, um... unless it's, it varies by food, can we just pick a very specific example like a peanut?

   6. KNKari Nadeau38:53

      Sure. Um, that's great. And we talk about peanuts in the US, Peter. Uh, I also wanna get back to your original question about the incidence and prevalence of food allergy. It's occurring throughout the world. It's not just a US problem. So peanut is also not just a US problem. It's, uh, th- those allergies are in, uh, the UK and Australia, but not in Italy, for example. In Italy, hazelnut is number one in terms of the-

   7. PAPeter Attia39:18

      Yeah

   8. KNKari Nadeau39:18

      ... the sh- the sheets. In Japan, it's fish. In, uh, China, it's milk. So we can talk about peanut today because it's an example of how our immune system reacts to something, but it's a very similar immune reaction to a child in Japan who has fish allergy or a child in, uh, China who has milk allergy or an adult in Italy who has hazelnut allergy. And I've seen a spectrum of allergies. I've seen people that have allergies to cinnamon. I've seen people that have allergies to orange pit seeds because all of these have proteins in them, so people can actually become allergic to these proteins. People have allergies to the tannin proteins from grapes in wine. So I'll tell about the story of the peanut, but I want people to know that it's not just about peanuts. And many people that have allergies to one food have allergies to other foods. So people also need to know that if they have a child with a food allergy, expect that it's highly likely that that child will develop another food allergy as well. So be super careful, but also super vigilant about taking, um, your child or yourself to the doctor to keep on getting managed and diagnosed. So you have a peanut, and we think that one of the reasons why people start to have food allergies, it's not genetic. 70% to 80% of the time, it's environmentally related. It's not related to genes in the family. So when a baby is born, perhaps their skin is a little rough and a little dry, and there might be microscopic holes in that skin. And that happens a lot now. A lot of children have dry skin, and we can talk about that [laughs] uh, another time. But with that little dry skin, that means the cells... The n- my two hands here are cells called epithelial cells. They're skin cells that typically are connected and they're with a nice, beautiful barrier. But unfortunately, with dry skin, they kinda separate. And our body doesn't know how to deal with this separation too well. It thinks it's like a mosquito bite. It's like, "Wait, what the heck's happening? I have a little hole in there." And so it reacts to these types of holes as if it was a mosquito bite. So all of a sudden in the air, you have dust that might contain hazelnut protein or, in this case, peanut protein. And that comes settling in, and it goes through this hole. And our body has a very prehistoric way of dealing with this, right? Back to those parasites. So they... it comes in by just passive, um, aeration. It drops down on the skin. The body tries to pick it up and say... and it tries to sense this, just like I explained in terms of the immune system. Those macrophage are like, "What the heck is this? Is this good or bad?" And then it says, "Wait, this is bad. This is not suppo- I'm not supposed to have food through my skin. I'm supposed to have food through my gut." So the cell takes it up and activates the allergic pathway because it thinks it's a parasite. It thinks it's a mosquito bite. So what happens is it takes it up and makes this molecule called IgE from that B cell. So the food gets taken up, gets processed. It teaches a T cell to interact with that food antigen, and then the B cell starts to make IgE against that very same food antigen. So the next time that baby eats a- That peanut, even if it eats it through the gut, that little IgE molecule will have been made by the B cell, and it's sitting around in the blood, and then it will bind to the peanut protein that the baby eats. And when it does, even though, like I said before, the IgE is a very small percentage of the concentration of proteins in the blood, it is such a potent molecule. And what I call it, it's the match that lights the fire behind allergies. So you have this peanut that otherwise for you and me, Peter, we would be able to eat, and we view it as nutritious. But in a person with a already given allergic reaction to peanut, that IgE binds to the peanut, and then this part of the IgE molecule, my arm, that sets into another part of a cell as a receptor. So it docks into the receptor after it binds to the peanut. And then that receptor on the cell surface activates histamine release of the cell, and that occurs within minutes. So the histamine goes through the body and within six minutes causes swelling, can cause mucus, and that mucus can be in your lungs, can be in your eyes, can be in your nose. And it also releases histamine. That cell releases histamine, and that histamine can cause itching on your skin. That's very similar to what would happen if you got a mosquito bite. You wanna itch. You wanna get rid of that mosquito. In the same way, the body's trying to get rid of that food. But unfortunately, you've already eaten it. It's already in your body. And so you see these reactions via IgE, and they release histamines. And in my mind, it's a very skewed reaction. The body's trying to do something that it was meant to do prehistorically, but it doesn't help the person at all. In fact, the histamine becomes so high that it can cause sometimes death. And within minutes, if you already have asthma, if you already have lung issues, that mucus can become so strong that it clogs up your lungs, and that's what oftentimes can lead to those very rare fatal reactions. Or there's another chemical called bradykinin that is released by these cells once that receptor docks, when the IgE docks into the receptor. Once that receptor tells the cell to release, it releases histamine and it releases something called bradykinin. That's another bad actor chemical. The bradykinin can affect our blood pressure system. That can lead to dizziness and can lead to heart issues. That's the second reason why people have fatal reactions. So you can imagine when you take epinephrine through an injectable epinephrine device, that helps both the lung clear the mucus, and it helps the heart and the blood pressure stay strong so that you don't have one of these near fatal or fatal reactions. But it all is linked to the immune system and how it reacts, and it's a very fast reaction.

   9. PAPeter Attia46:10

      Is my memory correct that the cell that's releasing the histamine is a mast cell? Am I remembering that?

   10. KNKari Nadeau46:16

       Good. I was hoping you'd ask that. So again, you're seeing both sides of the story for the immune system, the humoral response, which is IgE, and now the cellular response. So once that receptor gets docked into by the IgE, the cells that have that specific receptor on them are called mast cells. They're also called eosinophils. And for those of you sort of listening, there's another type of disorder called eosinophilic disorders, which, you know, that's a different type of food allergy, but also related. And then those mast cells exist in tissues, but they're not in the blood. Eosinophils are in the blood. The other third type of cell is called the basophil. That's in the blood. So this is such a potent system because it's got these cells ready to go in the tissues, the mast cells. Mast cells are in the skin, they're in the gut, they're in the lung, in the eyes, in the nose. And then you also have these other cells floating around the blood that are also secreting histamine and bradykinin. They're like the messengers across the whole system, and then you have the mast cells embedded. And the mast cells can live a very long sign-- time in tissues. So these basophils and eosinophils are in the blood. These mast cells can live a long time in the tissues. And that's why someone's reactions can build up over time sometimes because every time they eat that food or have that allergen exposure, their mast cells are gonna remember because of the immunoglobulins that bind to them.

   11. PAPeter Attia47:48

       I- is the implication, Kari, that each successive exposure gets worse? Um, and, and as a, as a sort of follow-up to that question, how often is a person's first brush with a food allergy a fatal one?

   12. KNKari Nadeau48:04

       Right. Excellent question. So we're only as good as our data. We're only as good as epidemiological studies as well. So, um, [lips smack] typically, and this is again typical, there's always exceptions. If you're-- if you learn about your allergies before the age of two, those food allergic reactions are typically vomiting and hives. They're not typically related to lung and heart. So babies, for example, although there are rare exceptions, toddlers and babies typically do not have fatal reactions to their first ingestion of food. But there's a lot behind this. So if you actually dissect out who dies and who doesn't die from a food allergy, it's typically people that already have a heart problem, already have a lung problem, or didn't get to the EpiPen w- uh, fast enough. So It would seem logical, like you're, um, inferring that with every dose that you take, your reaction could get worse and worse with the same dose. But it depends. It depends, for example, if you're at elevation. It depends if you already have a cold. It depends if you have aero allergies and you're allergic to a dog and a dog came by you that week and you also ate a peanut. So there's a lot that change that. But yes, in general, if all things being equal, each time you ate it, your immune system would remember more and more and would boost up that response. Now luckily, with therapy, there's a way to retrain your immune system, but that takes regular interaction with the food every day, not every week. If you take it every week, it actually boosts your immune system to become more allergic.

   13. PAPeter Attia49:51

       Yeah.

   14. KNKari Nadeau49:52

       Take it every day. So there's something to the circadian rhythm and the diurnal cycle, which we haven't talked about this yet. But what I love about the immune system is it can be trained and you just need to know how to train it, and you can train it away from becoming allergic and, uh, and train it into becoming more protective.

8. 50:11 – 1:05:02

   The role of environmental factors in the onset of food allergies and strategies for prevention

   1. PAPeter Attia50:11

      Well, I, I absolutely wanna focus on that because it's, you know, I think the most hopeful aspect of all of this. But I wanna kinda go back and understand more these environmental factors that are predisposing, uh, children and adults to these factors. So you mentioned one, which was dry skin. Again, I, I can only imagine after listening to this, everyone is gonna be lathering up themselves and their children, and we're gonna have the, you know, we're gonna, we're gonna make L'Oréal or whoever-

   2. KNKari Nadeau50:40

      Yeah

   3. PAPeter Attia50:40

      ... makes nice skin lotion very, very happy.

   4. KNKari Nadeau50:42

      Yeah.

   5. PAPeter Attia50:43

      Um, ca- can you say... Are, are there any other factors that, that we've identified that seem to be predisposing people?

   6. KNKari Nadeau50:50

      Yeah. Um, and there's some factors if they're lacking, they also predispose people. So people have talked about having good microbiome, good dirt, and that helps sort of decrease the likelihood of food allergies. Children who grow up on farms, for example, have, uh, a really good exposure to animals. They tend not to have as many food allergies, interestingly enough. So I call that the dirt hypothesis. Um, also growing up with a lot of animals like dogs also helps, uh, reduce the likelihood, and that's probably due to the microbiome. But importantly is vitamin D seems to also play a role. So having enough vitamin D in your blood also decreases the risk of food allergies. Um, being around too much detergent, that's what I call the dry skin hypothesis. Unfortunately, a lot of our clothing being washed in detergents, our dishwashers having really potent concentrated detergents these days, it's not getting rinsed away enough so that the skin in babies, it heals so well, but it is somewhat more sensitive than, let's say, adult skin. And so because of that, they tend to have dry skin due to all these other issues. And let alone detergents, but also any time in life, whether or not you're a child or a baby or, or an adult, if you have pollution or tobacco smoke, that also causes dry skin and itchiness. Uh, not just the skin on the surface, but also in your body. So it's not... The anything that touches the air has skin cells. So that means our lungs, that means our gut. So all of these features that I talked about can affect the skin. And through... We think that through the skin allergies can begin. Um, it's not the only hypothesis. We also think that it's really important to make sure that when you look at your overall diet, that you diversify that diet really early and often, so that if you can take certain proteins and feed that to your children when they're young and have that diversity in the diet, that that can actually prevent the advent of food allergies later on in life. So we talked about dirt, we talked about dogs, we talked about detergents, we talked about vitamin D, and we talked about diversity in diet. So I call that kind of the Ds. Um, but importantly, that dry skin does seem to be a conduit by which food allergies start. But what I didn't say was DNA, and that's important because a lot of parents, a lot of people will say, "Oh, my parents gave this to me," or, "I'm gen- I... This is in my genes, so there's no way I can do anything about that." And that's not true. So there are certain allergies that can be passed on from one generation to the next, but even those diseases, if you change your behaviors, that can also improve and decrease the likelihood of having food allergies. So, so I hope that was helpful. When people do listen, I hope when they do try to improve their skin barrier, if there is an emollient you can buy, try to stay away from the emollients that are based with petroleum products or paraffin products or Vaseline. Because what science has now shown us is that because those are not natural to the skin, our skin doesn't really like wax or petroleum products or Vaso- Vaseline is a petroleum product. That tends to increase the bacteria on our skin, and that can make overall the skin inflammation worse. So try to choose products that have natural lipids that give the skin back what they're missing.

   7. PAPeter Attia54:31

      A- And, and how, how does one look for that on the label? What, what would be the signs of that?

   8. KNKari Nadeau54:36

      Great, great question. The natural lipids are like ceramide. So I don't work for any companies. I don't really know which companies have ceramide, but I know one company, CeraVe, has cer- has ceramide in it. So try to look for those, um, emollients that actually replete the skin with what it is depleted from, which are its natural lipids. And then also try to rinse things. Now we are in a water shortage, and we have to be careful too, uh, with not using too much water. But if you can, choose ecologically friendly detergents because eco-friendly detergents, eco-friendly foods tend to be better for our own bodies. And I'd love to know your own opinion about that, Peter, but that's what I typically tell my patients. Try to avoid detergents that are not eco-friendly because they're probably not so friendly to your body.

   9. PAPeter Attia55:30

      Wanted to ask one other question about this. Any relationship with breastfeeding? You mentioned it earlier with respect to IgA. Uh, does, does a child who's breastfed or not breastfed, do we see any difference in the incidence of food allergies?

   10. KNKari Nadeau55:43

       Yes. It's a great question. So there have been a lot of my colleagues in Europe that have tested this. Now, because breastfeeding is now, uh, s- so much the standard that it's hard to do these studies now because the World Health Organization has recommended, you know, breastfeeding, which is wonderful, and that's really important to start feeding infants other types of foods between four to six months of age. But in general, breastfed infants do do better in terms of their overall gut health, in terms of their overall health in general, but it has not been shown definitively that by breastfeeding you can prevent food allergies. But it is very helpful towards creating an overall healthy immune system. So I, in general, tell all my families, "If you can breastfeed, please do." But the ulterior, unfortunately, is that some children have... It's very rare, but they can have an allergy to a protein in the mom's breast milk.

   11. PAPeter Attia56:41

       Hmm.

   12. KNKari Nadeau56:42

       So if your child does start to have issues with your breastfeeding, go see a doctor and then see and make sure that they don't have an allergy to your own milk. But that's very, very rare.

   13. PAPeter Attia56:53

       And nowhere in that discussion of the Ds did I hear, um... Well, I guess, yeah, you talked about diversity of diet, but I wanna talk specifically about the, the, the antigen, right? So what is the case for and against early exposure to nuts as a vehicle to prevent the, um, the, the onset of one of these allergies? Again, I, I think about the last 15 years. I feel like I've heard pediatricians go in various directions on this. At first it was... And I think about this through the lens of my kids, right? So it's like sometimes we were told, "Absolutely don't let them see a nut. Don't, don't have nuts in the house for the first two years," to, "Hey, make sure they're eating nuts and peanut butter." And, and so, so where are we today on that?

   14. KNKari Nadeau57:40

       I agree, Peter. It's been confusing. There's been a lot of flip-flopping, and unfortunately, there were well-meaning people 20 years ago that made guidelines based on not a lot of data. I think that people were seeing there was an increase in food allergy throughout the world, and that's probably due to many different things, but that they reacted in a way to say, "Oh, we don't have enough science, but we're really worried, so let's just tell people to avoid those foods, and hopefully that can prevent this epidemic from increasing." And unfortunately, the minute those guidelines came forward, and it was also during the time that I was raising my kids, um, the minute those guidelines came forward, you started seeing a hockey stick in the epidem- in the epidemic. It actually started to increase. In those countries that did not follow those guidelines, it stayed flat.

   15. PAPeter Attia58:33

       So that's a ve- that's a very telling case, even though it's not a randomized intervention, that says when you avoid foods at a young age, you paradoxically predispose to the allergy.

   16. KNKari Nadeau58:46

       Exactly. So let's talk about that, right? Because we talked about the importance of guidelines. I agree. They're very important, and oftentimes guidelines are made by people that really think hard, and they use the data that's at hand. But we're only as good as our data. So fast-forward 20 years afterwards, the world had different data. The world said, "Wait a minute. We now think that through the skin allergies begin. Through the diet, allergies can stay quiet. We now know that the gut is really important for tolerizing to those antigens." The, the immune system in the gut is meant to tolerize. The immune system in the skin, in our lungs and in our skin-skin, is actually meant to be activated and react. So when you think about that dry skin hypothesis, of course it's gonna be promotional of allergic pathways, but when you think about taking things through the gut, it's gonna be promotional of tolerogenic pathways. So we learned a lot in the last 20 years. So when the same people came together and wrote the guidelines 20 years afterwards, they said, "Wait a minute. It's very clear now," and many guidelines have changed, Peter, now to say we need to diversify the diet. We need to tell our country's population to start having children eat foods in small amounts, like tree nuts, like fish, like milk, like egg, like peanut, and to be able to have that early and often and regularly so that we can try to prevent food allergies. So that's the general mantra. The guidelines have now switched. Same thing for people who are pregnant. It used to be thought women who are pregnant, based on a very small study, only 20 individuals, but that was the only study that was available 20 years ago, that those pregnant women should avoid peanuts and tree nuts. But actually, fast-forward 20 years after, there was a much bigger study done, and that showed that definitively it's okay to have peanuts and tree nuts when you're pregnant. It's actually healthier with omega-3s. Of course, people who already have food allergies shouldn't be eating these foods when you're pregnant or if you're a child. But in general It's a way to prevent food allergies now, among many other things like we talked about. But it does seem to be important, and it goes back to those instrumental recipes of the immune system. If you, if the immune system can probe the antigen, know that it's safe, know that it's not gonna harm the immune system or the body, it then becomes tolerant. But in order to give it that instruction sheet, in order to give it that recipe, you need to feed and you need to get exposed regularly. And we think regularly means every day to every other day. And you'd say, "Well, wait a minute. Why? My grand- my grandmother didn't have to feed me these foods, or my mother didn't have to feed me these foods regularly. What all of a sudden changed?" And we think that the environment is changing. We know, you know, the environment is changing all around us, unfortunately with different detergents, with different emulsifiers, with different chemicals in our food, with different pollutants, with different viruses. It's changing. So now we take the science and we have a better instruction sheet for patients, and I'm grateful for that, but it is all based on evidence.

   17. PAPeter Attia1:02:05

       Do you think the genie ever gets back in the bottle? Do we ever get back to the levels we had 30 years ago? Or do you think that even if we can get dietary practices to where we were, which is to say we're at a place where parents are encouraged to liberally, uh, and diversely, you know, sample food for their kids, these environmental issues, uh, the detergents, the dryness of skin, all those things, the low vitamin D, presumably because kids are playing outside less these days and they're, you know, indoors more, and all, all of the things that we understand, uh, that it never quite gets back to the level it was when I was a kid. Like I gotta tell you, when I was a kid, um, Kari, I didn't know an-- I did not know another child that had a food allergy, okay? So, um, all through, all through grade school, middle school, high school, there was not another child in my zip code that had a food allergy. Today, my kids can't take nuts to school. It's, it-- You can't have nuts on an airplane today. So it's-- I can't tell how much of this is overreaction, just sort of... Y- you know, anyways, so there, there's clearly a log fold change, but I can't tell how much of it is, is also just a, a disease of the brain, you know, if that makes sense.

   18. KNKari Nadeau1:03:16

       No, but you're right to ask that. But... And lots of epidemiologists have now tested it. It's real. I mean, this is not just people thinking they have allergies, and when you and I were growing up, they didn't. Like, this is real. There were people, very rarely, that had a milk allergy, peanut allergy, but the allergists never really focused on them. Now, the typical allergist, and we have allergists that have worked in the community for 80 years, right? Their offices have shifted from being offices where aeroallergens were what they took care of all the time to now it's foods. And that's not because someone thinks that they're allergic to food. This is a real diagnosed food allergy. And I think your, your question is a good one, but I don't think we're ever gonna get back to 30 years prior because we have different practices where-

   19. PAPeter Attia1:04:04

       Mm

   20. KNKari Nadeau1:04:04

       ... we have different ways of processing food, different environmental exposures. We-- Because this is mostly environment, if I have identical twins born to the same mom and dad, I can have one twin develop a food allergy and the other one doesn't, and typically that's in adulthood. And the one twin that develops a food allergy, they're the ones that have been out in pollution more. They've eaten n- not such a healthy diet. They have a lot of preservatives or they smoke. Uh, and so-- or they eat a lot of fast food. Like it's so-- Or they are, uh, under a lot of stress, and they don't get a lot of sleep. So genetics being equal, exposures in early life being equal, there are certain behaviors that now we're seeing are more associated with food allergy, like air pollution, and I don't think we'll ever go back. But luckily, science has helped us so that we know what to do now and how to change our behavior so that we can try to prevent food allergies from worsening.

9. 1:05:02 – 1:26:21

   How immunotherapy helps to overcome, and even cure, food allergies

   1. PAPeter Attia1:05:02

      So let's now talk about the work that you've been kind of... Well, I'd like you to put the context around your role. I mean, of course, I think of you as pioneering this work. I'm sure you'll, uh, elucidate us all with how many people are pioneering this work. But, but you, you and I met, like I said, about a decade ago through a mutual patient of mine who at the time was being treated by you. And, uh, you know, quite frankly, I was just sort of blown away at the fact that a person who once had an anaphylactic reaction to nuts was going through an immunotherapy-based sensitization program with you at Stanford, and then all of a sudden didn't have an anaphylactic reaction to nuts. This was mind-boggling to me, and I'm forever in your debt for graciously hum-- you know, letting me wander around your lab and sitting around chatting with me over coffee. So, um, c- can you give us a bit of a sense of, you know, what this revolution is about and, and... 'Cause it, it really is. It's, it's, it's sort of hard to wrap our head around when you consider the lethality of these conditions.

   2. KNKari Nadeau1:06:06

      Right. And, um, and we take this so seriously, and, and that particular family has been so engaged, like so many other families, that this is a disabling disease. Uh, my colleague Kim Yates, you know, has done so much work in this area, as well as other families, to be able to educate. And organizations like FARE and others have really moved the needle forward. So when you think about food allergies, it becomes in a child's mind or an adult's mind something they have to live with, and it's not fun, and, um, it can affect their social lives, their quality of life. So they come to the table often wanting to know what's the best therapy now. And compared to when we started with your patient, we have a lot more therapeutic options, and that's always good in any field to have options, especially for our patients. So any of these decisions that I'll talk about today, they're really personal. They're really something that the doctor, the healthcare provider should talk to the patient about and see what's the best for me. But in general, again, getting back to that immune system, getting back to the regular eating of foods so that you can start retraining it to tolerize to those foods, to see them as natural and not unnatural. This has been going on for about 100 years, and even though to us and to many others this is something new, and we did work at Stanford, but actually other work at other institutions in the country and other work in Europe had already been done. So what I was doing is building upon other evidence and clinical trials that had been done, and I worked very closely with the Food and Drug Administration, the FDA, because you don't wanna do anything that's not safe and that you wouldn't wanna do for your own children if they had the disease. So with that in mind, I learned a lot about the immune system. What you do in immunotherapy at the very basic level is give the person back the very same thing that they're allergic to, and this was done 100 years ago with dog allergies, with cat allergies, with grass allergies, with mold allergies. People would actually start to take these things but inject them, so like a, a lot of your patients might have done allergy shots when they were little. But those are ways that we've learned as immunologists that, oh, you can retrain the immune system. You can train a body so that they are no longer allergic to cats, for example, but you need to keep taking those allergy shots in general. So the same thing for food. You don't wanna give a food allergy shot because the food in, in and of itself is very potent, and because it's a very specific IgE-mediated disease, foods, if injected into you, can be extremely dangerous. So we don't give it via injection.

   3. PAPeter Attia1:08:54

      But just to be clear, the, the, the allergy example, [lips smack] um, let's say it's cat, you know, dander or whatever, is the shot giving you a little bit of that dander? Is it sensitizing to you a little bit a- And, and how frequently does a patient need that to i- i- to achieve a s- a symptom-free existence?

   4. KNKari Nadeau1:09:12

      Exactly. Initially, you need to take it, like, almost daily. Daily to a week. And then once your body starts to build up that immune muscle, you only need to take it about once a month.

   5. PAPeter Attia1:09:24

      But you will do that for life.

   6. KNKari Nadeau1:09:26

      Well, some people do it for life. Some people do it for five years. If you stop it after five years, you have a 25% chance of regaining your allergy.

   7. PAPeter Attia1:09:35

      Wow.

   8. KNKari Nadeau1:09:35

      You have another 25% chance of having it just be less, but there. And then you have a 50% chance of having it be resolved for the rest of your life, but you need to be on five years of immunotherapy, depending upon the aeroallergen, and we're talking environmental allergies.

   9. PAPeter Attia1:09:52

      Yeah, and is the reason that you can get away with doing that because it does not induce anaphylaxis-

   10. KNKari Nadeau1:09:59

       Exactly

   11. PAPeter Attia1:09:59

       ... in the way that the food does? So it's just the severity-

   12. KNKari Nadeau1:10:01

       It's different

   13. PAPeter Attia1:10:01

       ... of the IgE mast cell reaction.

   14. KNKari Nadeau1:10:04

       Exactly. Exactly.

   15. PAPeter Attia1:10:06

       Okay.

   16. KNKari Nadeau1:10:06

       And we still are trying to understand why that is. Why is grass allergy not as bad as peanut allergy? Um, so people are still trying to figure that out. Like, why is dog allergy-

   17. PAPeter Attia1:10:18

       Mm

   18. KNKari Nadeau1:10:18

       ... not as bad as peanut allergy? But given that it is, for immunotherapy, like we said, you give small amounts of that specific allergen back to the patient, whether or not it be a shot for environmental allergies or whether or not it be orally for a food allergy. You give it back in small amounts. You start with a small speck that you can hardly see, and then you increase that dose by 25% every two weeks, but you're giving it every day, and then you increase it step by step. Every two weeks, you increase the dose, but you're giving it daily, and you wanna do that in a doctor's office. You wanna be really careful about that, so we did it in our clinical trials. And over time, you readjust the immune system. Now, it takes a while, right? This person has had their allergy, and it's been quite, um, severe for them, so to retrain the embedded memory aspect of the immune system takes time. And what happens over time in the immune system is those little T cells start to be taught that, "Oh, wait a minute. This antigen, it seems okay. I'm getting it every day. Boy, I need to readjust myself. I need to reframe, frame my mindset." And instead, T cells start to reframe their mindset. You start creating another whole layer of memory T cells that become tolerant to that antigen, and then they tell the, they teach the B cell to forget making IgE. In fact, we want you to make more IgA. We want the B cell to make more IgG because that's protective. And so that's what happens over time. During the first year of immunotherapy, you're slowly going up. You're slowly readjusting, and in our patient's case, that's exactly what happened. That person was readjusting their immune system, readjusting their immune muscle to then switch from an IgE-mediated bad reaction to instead creating protective molecules that could protect the patient against the allergy. The IgE can still be there, but you have this huge amount of protective, what I'm gonna call blanket, so that that IgE doesn't have anywhere to go. When it wants to bind to the receptor, that blanket of immunoglobulins don't allow it to bind to the receptor. We all have IgE.

   19. PAPeter Attia1:12:48

       How, how-

   20. KNKari Nadeau1:12:48

       All of us do, but some of it works, and some of it doesn't.

   21. PAPeter Attia1:12:52

       In the case of the person with the anaphylactic reaction to peanuts, do they ever go above the .005% IgE concentration, or is... Yeah, and how high does it go, just for comparison?

   22. KNKari Nadeau1:13:04

       Yeah, good question. So IgE is typically specific. You have to have an IgE to a specific food to be able to have that reaction. And yes, typically some people with peanut allergies will be over that .005%, or anyone with allergies. Their IgE is higher. And just so that you know, a virus can also increase IgE non-specifically. Your body just starts making IgE, probably against the virus. So it's a very prehistoric type of reaction. But importantly, Peter, for every IgE molecule, we can make 100 IgG molecules that protect against that IgE molecule circulating and becoming potent. And that's what's happening during the time of immunotherapy. You're making a huge amount of IgG molecules to bind against that IgE becoming what I call pathological. So it's a ratio thing.

   23. PAPeter Attia1:14:03

       And just give me a sense of scale. So on the very first cycle, that first two-week cycle, what fraction of a peanut is being given in the capsule? How, how small is it? I'm sure it's less than a single peanut, obviously.

   24. KNKari Nadeau1:14:18

       Yeah. It's about 1/200 of a peanut.

   25. PAPeter Attia1:14:23

       Wow.

   26. KNKari Nadeau1:14:23

       1/200. You start very [laughs] low, and you go very slow. Because in the end, you wanna retrain that immune system, but you don't wanna activate it too much. Now, during that retraining, sometimes your muscles get sore, right? Sometimes you will see some hives. Sometimes you will get a little itchy throat. Your body will have these little reactions, but I call them simmering reactions. But you do need to take it every day. And then you start to see this switch from IgE to IgG. And again, the T cells are responsible for that. Many other cells are, too. But in general, if you stop the therapy, this beautiful pathway of tolerance then starts to go back to the original pathway. So it's, it's really protection, the... It's very rare that a person completely flips and becomes non-allergic. Does that make sense? It's really what you're doing in the immunotherapy is changing your threshold and creating more protection molecules around you and creating more protective cells around you.

   27. PAPeter Attia1:15:30

       And when does that switch flip typically?

   28. KNKari Nadeau1:15:34

       Yeah, typically, if you're on the typical immunotherapy regimen, it flips at around nine months to a year.

   29. PAPeter Attia1:15:40

       And again, just to give people a context of the doses we're talking about, someone comes in with an allergic reaction to peanuts. For two weeks, they're gonna take a capsule that contains 1/200 of a peanut. If that goes according to plan, they will increase that by 25% for another couple of weeks. So a month into this thing, they're still basically taking 1/200 of a peanut.

   30. KNKari Nadeau1:16:04

       [laughs] Yeah.
10. 1:26:21 – 1:28:03

    Can immunotherapy work for environmental allergens like pollen?

    1. KNKari Nadeau1:26:21

       that we've tried to.

    2. PAPeter Attia1:26:22

       Um, going back to sort of the environmental, um, allergies, so, you know, here in Austin, we have this thing called cedar fever, right? So the cedar trees give off a ton of pollen, and, uh, you know, knock on wood, um, fortunately, it hasn't afflicted me. But I know so many people here who for a period of, gosh, I think it's sort of December, January, or November, December, January, where, I mean, they can't function without Benadryl and Zyrtec. Um, I've asked around on behalf of friends to see if there are immunologists and allergists here that have an immunotherapy regimen, and to my surprise, nobody does. W- Would this be con- would this be an easy thing to address?

    3. KNKari Nadeau1:27:03

       So cedar allergies are interesting 'cause the cedar protein itself is something called a, like, it, it's a protease sometimes, so it can start to grade proteins. It's a little weird. But cedar allergies are very serious. And yes, there are people that have developed immunotherapy for cedar. So it's interesting that no one around there-

    4. PAPeter Attia1:27:24

       It's interesting that I can't find them in Austin, but-

    5. KNKari Nadeau1:27:26

       Yeah, exactly

    6. PAPeter Attia1:27:26

       ... I'll have to, I'll have to connect with you offline-

    7. KNKari Nadeau1:27:28

       Yeah, sure

    8. PAPeter Attia1:27:28

       ... for this 'cause I-

    9. KNKari Nadeau1:27:29

       Because-

    10. PAPeter Attia1:27:29

        There are a lot of people here who I know would be interested in that.

    11. KNKari Nadeau1:27:31

        Yeah, it's the same rubric. You can desensitize to it, although it takes a little bit, you know, a lot of care, maybe that's why. But importantly, cedar allergies are something, just like other tree allergies, they're really to be cared for, and they can, um, give you lots of mucus and asthma. So I hope that those individuals you take care of can get some benefit. But immunotherapy, so I call it proactive therapy and reactive therapy. Reactive therapy are all those antihistamines people need to take.

    12. PAPeter Attia1:27:59

        Yeah.

    13. KNKari Nadeau1:27:59

        Proactive therapy is the immunotherapy to readjust your immune system, but you need

11. 1:28:03 – 1:40:40

    Air pollution: impact on health and tips for reducing your risk

    1. KNKari Nadeau1:28:03

       both.

    2. PAPeter Attia1:28:04

       I wanna now talk a little bit about, uh, air pollution just for a moment. Um, tell folks what, what's a PM2.5 and why should, why should somebody care?

    3. KNKari Nadeau1:28:14

       Yeah. You know, 10 years ago, I didn't really understand all of the PM2.5 jargon either, so I wanna just make sure, in all humility, this is something that we all need to learn now, every single one of us, even if we're in a research station in Antarctica. Because air pollution, unfortunately, is rising. Um, we need to know that there are no boundaries. When wildfire smoke happens in Australia, it can circumnavigate the world within four days. And PM2.5 is a way that we, as a society, have given a measure to air pollution, but it's not everything in air pollution. It's particulate matter. It's the particles in air pollution that are 2.5 microns in size. Now you think, "Well, what in heaven's name is that? Like, 2.5 microns, what does that mean to me?" Well, if you think of, like, a little red blood cell, that's a micron. So you think about particles that are basically about twice the size of a red blood cell, and those are floating around in the air. And why do they do that? Well, that's because partially combusted fuel, combusted fuel from our cars, if you don't have an electric car, combusted fuel from industry. When it breaks up petroleum, when it breaks up any kind of product, wood fire as well, little particles escape into the air, and those particles are not what you see as soot on your car. They are not what you see as brown dust on your, uh, uh, on, on your house. These are particles that are so small, they continue to be aerated, and they can float in the air around the whole world, and they're so small that they can penetrate into our lungs. And why do we care about that size, the 2.5 microns? That's because it can get through our lungs and into our blood. And w- it's dangerous also because PM2.5, as a def- as a defined measure of air pollution, has about 200 different chemicals in it. 200. And of those 200, some of those are what we call volatile organic compounds. These are compounds that you smell when you smell, like, uh, markers like xylene or, in the old days, mothballs, naphthalene. So these are chemicals that are not good for the body. They are from combusting fuel. If anyone of your listeners is a chemist, these are what we typically called six-membered rings. They're organic chemists' sorta nightmares 'cause they smell horrible, and I didn't like them when I was doing organic chemistry when I was a student. I don't like them now because now I know what they can really do to your body. They can cause cancer. They can increase asthma. They can increase cardiovascular disease, stroke. And wildfire smoke is even more potent as an air pollutant than PM2.5. We also measure PM2.5 for wildfire smoke because wildfire smoke basically is biomass burning. But unfortunately, wildfires aren't burning just trees anymore. They're also burning commercial buildings. So what goes up in wildfire smoke compared to, let's say, just diesel from the car, which is bad enough- But in addition, with wildfires, you're burning up your upholstery, you're burning up your paint thinners, you're burning up your detergents underneath your sink, your shampoos. That's all going up in the air, and that's also measured as PM2.5 because all those particles are so small. They're also going into your lungs. So with wildfire smoke, we also have to be super careful. So for any person that's getting exposed to any PM2.5, you can look on websites, you can go look at AirNow, you can go look at the NOAA website and know in your region what air quality index you have that day. If it's in the green zone, great. If it's in the yellow zone, please start wearing a P- a mask, a two-point... A, basically a mask that you used to wear in COVID, because those masks are very important to reduce the risks of those exposures to your lungs, especially for children and elderly patients. So that's what PM2.5 means, and I want people to really understand that it's measurable, it means something biologically that's important, it means something medically, but it also can be measured by well-meaning agencies like the EPA, like we use in California something called PurpleAir, and you can actually look on the web. The PurpleAir monitors can actually tell you what PM2.5 measurements are in the air. Not all countries have that. We're lucky in the US that our US agencies measure PM2.5 on a regular basis so that we can map that to our zip codes. But I think all people need to be more aware of that.

    4. PAPeter Attia1:33:14

       Do, do you recommend that people... Yeah, 'cause there's a lot of, uh, PM2.5 monitors that you can buy for your own home. Is it necessary, or do you feel that if you are just looking at these databases, you get a good enough sense? Because I can't tell which problem they're solving for. Are they basically trying to say, "You need to make sure you don't have particulate matter in your home, because if you do," by the way, it might be that you have, you know, a leaking stove or, I mean, that would probably turn up as carbon monoxide or something else, versus, "No, you just need to know what the level is outdoors, because that might be the day you choose not to do your 10-mile run if it's, you know, a r- a red day"?

    5. KNKari Nadeau1:33:51

       All, all, all those things. So first of all, if you know that you have to be outdoors and you're an immigrant farm worker and you have to be out there for eight hours no matter what, and the air quality index is 100 like it was yesterday here in California and we had people out in the fields, they should know that they should wear an N95 mask, period.

    6. PAPeter Attia1:34:11

       An N95 will sufficiently prevent, uh, PM2.5s from getting in?

    7. KNKari Nadeau1:34:17

       Not perfectly, but at least it reduces the risk. No mask completely reduces those small organic molecules, those six-membered rings from getting through the mask, but at least it's better than nothing. So typically, that's what I'll say. I'll s- And I'll definitely say to my, to my patients, "Please don't exercise during any air quality index that's greater than, let's say, 50," 'cause that can... Even though they might not feel it during the hour that they exercise outside, it definitely affects their immune system. There were studies done in, uh, in London, for example, where people would exercise out in the streets that had a certain air quality index. And in London, you can actually do this because there's micro, uh, PM2.5 measurements in Hyde Park versus in Broad Street. So they did this research, and they knew that even if people exercise out for one hour in clean air versus polluted air, their immune system changed for a whole day-

    8. PAPeter Attia1:35:12

       Hm

    9. KNKari Nadeau1:35:13

       ... based on that one hour of exercise. So I would say be careful. And yes, indoor air is very important. We... Our lives are spent indoors for more than 90% of them. That means 90% of the time that we're on this planet, we're spending it indoors. That's typical for the average US citizen. So having a PurpleAir monitor indoors is actually helpful, especially if you live in a place with lots of wildfire smoke or air pollution, because you can't assume that your air pollution is being filtered appropriately, and you can't assume that you're being protected, 'cause just because oftentimes you can't smell this and you can't see it, it, it is so small that you need a special detection monitor to know if it's there. Now, if you do have bad indoor air, you can buy a MERV filter. You can buy a filter in your air conditioning or central air, or you buy a standup filter to reduce the exposure. So all these things are available to people, and in certain states, they are available freely for families that can't afford them.

    10. PAPeter Attia1:36:21

        So just to be clear, let's say you, you do this exercise. You buy the Purple filters. You figure out that, hey, actually, either, A, I live in a, in an area where there's enough pollution outdoors, and of course, it's eas- easily able to get indoors through windows and doors, um, or just for whatever reason, there's something in the house that's producing these compounds. Um, y- option one is you just get standup HEPA filters for the house, but you're saying option two is there are certain filters you can put in your HVAC that will do the same thing. And what are those called again?

    11. KNKari Nadeau1:36:52

        They're called MERV, and they're MERV, they're MERV 13 or higher. Don't buy a MERV 7 or 8. MERV 13 reduces all of the major PM2.5 as well as pollens, as well as other chemicals. But you need to change them often because they're getting clogged up. So if you can buy... And it's not... I don't work for PurpleAir, but you know, you can buy any of these monitors that can monitor external outside air and indoor air, and you can buy them and get to know the difference and how well your... You know, it's good to ventilate your home, so you don't want your home to also, like you said, be collecting its own toxins, and that can happen if you have a gas stove, for example. So, or a wood stove. So yes, in general- Knowing and measuring your PM2.5 is going to be helpful to your health because you can manage accordingly

    12. PAPeter Attia1:37:46

        Do, do you have a sense, 'cause I've never been able to get a great answer to this question, Kari. It's actually one of the reasons I did not include this in my book. So I wanted to include a section on air pollution in the book, um, and in the end I didn't for a couple of reasons, but the, the m- biggest reason was I couldn't get a really clear sense of the mortality impact. Um, a- and I couldn't, I couldn't quantify it the way I could quantify it for, you know, smoking, obesity, and some of these other things. So coupled with the fact that the book was already about-

    13. KNKari Nadeau1:38:17

        Yeah

    14. PAPeter Attia1:38:17

        ... 50% longer than anybody-

    15. KNKari Nadeau1:38:18

        Mm-hmm

    16. PAPeter Attia1:38:18

        ... wanted it to be-

    17. KNKari Nadeau1:38:20

        Yeah

    18. PAPeter Attia1:38:20

        ... um, but do, do you have a sense of the magnitude of this and-

    19. KNKari Nadeau1:38:25

        Yeah

    20. PAPeter Attia1:38:25

        ... you know, for example, like what's the difference between... A- again, e- even-

    21. KNKari Nadeau1:38:30

        Yeah

    22. PAPeter Attia1:38:30

        ... quantifying the exposure is a little difficult.

    23. KNKari Nadeau1:38:31

        Yeah.

    24. PAPeter Attia1:38:31

        It's not like, uh, pack-

    25. KNKari Nadeau1:38:33

        Yeah

    26. PAPeter Attia1:38:33

        ... years of cigarettes where we can say 40 pack year history versus zero pack year history translates to this much difference in, in outcome.

    27. KNKari Nadeau1:38:40

        Yeah. Actually now, Peter, you can. So, uh, there was a recent, the, the WHO just put a report out, the AQLI just put a report out from University of Chicago. I'll send it to you. Um, I wanna make sure you have this because you have such a wide, amazing opportunity to influence people through your bandwidth. And Peter, I f- I feel like you are in this incredible position to make this impact with others. You are a trusted voice, and because of that comes the privilege of being a trusted voice, but also that accountability and responsibility of knowing all the science. And so what I'll do is send you this report because it has now been put into exactly those terms, and it's more dangerous than tobacco smoke because it is so prolific. Uh, and I'll give you this report because in the first page, um, it, it shares with you the context of how pollution has killed about 8 to 10 million people a year now. And so, and that's attributed directly to air pollution.

    28. PAPeter Attia1:39:47

        And what is the final common pathway? Is it majority through cardiovascular disease, cancer? Where, where do we think the, the actual, uh, mortality comes from?

    29. KNKari Nadeau1:39:58

        Exactly. Uh, especially in low to middle income countries, it's, uh, it's cardiovascular disease and lung disease. In, uh, in quote unquote, more Westernized countries, it's more associated with stroke, long-term cardiovascular disease, and cancer. So I'll send you this. I'll, I'll get it for you, Peter-

    30. PAPeter Attia1:40:19

        Yeah, please
12. 1:40:40 – 1:46:12

    Resources for those wanting to learn more or find clinical trials related to food allergies

    1. PAPeter Attia1:40:41

       Well, Kari, this is, this is very interesting. I know we were a little bit short on time today, so I'll, I'll kind of just ask you one final question. We-- When you go back to the, that child who died in the ICU, the, the child who was kind of your patient zero, um, you alluded to it, but we never really got to it. Tell me, why did the EpiPen not work? When that father asked you about that, what, what was, uh, what happened there?

    2. KNKari Nadeau1:41:04

       They hadn't renewed the EpiPen. It had expired. They hadn't gone to the doctor for at least five years, and they assumed that their child had grown out of a milk allergy because that's what people told them would happen. But they never got their IgE retested. They never went back to their allergist, and so they still had the EpiPen that had been given to them five years prior, and it had expired. In addition, it was for a different weight. It was for Epi Junior, and he had gained and of course grown. So if he were to even get an Epi that was not expired, he should have gotten a different dose. So it interlaid all these aspects about the fact that you cannot know just what typically happens to a patient. If that happens to you, you need to actually go to a doctor and get your own set of data to figure out how to best manage your disease. It also taught the lesson of you've got to keep updating your EpiPen and making sure that it's renewed and not using an expired chemical or of any expired drug. And then lastly, that as you grow, you need a different dose.

    3. PAPeter Attia1:42:13

       Wa- wasn't there a big controversy a couple of years ago when a, a company that was selling EpiPens-

    4. KNKari Nadeau1:42:19

       That's right

    5. PAPeter Attia1:42:19

       ... decided egregiously for no apparent reason other than just malicious greed-

    6. KNKari Nadeau1:42:24

       Yeah

    7. PAPeter Attia1:42:24

       ... to jack the prices up? H- has that resolved, and are EpiPens now relatively inexpensive again?

    8. KNKari Nadeau1:42:30

       That's right. That company was Mylan, and they were making EpiPens, and that's why I called it injectable epinephrine device because now there's a lot of them. Thank goodness sort of-

    9. PAPeter Attia1:42:38

       Mm-hmm

    10. KNKari Nadeau1:42:38

        ... the FDA, other agencies got involved and said, "Okay, this is not right. You cannot keep charging that enormous amount of money." And so then what we call generic epinephrine devices started to be made. Other companies started to hit the road. There's other, uh, devices now that can be used called the Auvi-Q. So I think luckily now, thanks to many industries involved in this, there's also potentially a nasal Epi that can be used. So yes, that company, um, was seen as, uh, providing methods that were not ideal at all, and that was stopped, thank goodness, because no one should be charged that amount of money for a life-saving drug.

    11. PAPeter Attia1:43:20

        What were they charging for EpiPens?

    12. KNKari Nadeau1:43:22

        Oh, it was like four hundred, up to six hundred for some of my patients. So that luckily now is being covered by insurance, but again, third party payers also need to make sure that they can reimburse for these life-saving medications.

    13. PAPeter Attia1:43:36

        Well, Kari, this is, this is really interesting stuff. I, I think Look, I've learned a lot today, certainly getting the differences in some of the immunology here. Um, a- also, uh, I think the, the PM2.5 story is something that I look forward to digging into a little bit more.

    14. KNKari Nadeau1:43:51

        Yeah.

    15. PAPeter Attia1:43:51

        Um, especially as someone who does spend a lot of time outside. M- maybe no more than 10% of the time like anybody else.

    16. KNKari Nadeau1:43:57

        [laughs]

    17. PAPeter Attia1:43:57

        But it seems like I spend more time outside.

    18. KNKari Nadeau1:43:59

        Yeah.

    19. PAPeter Attia1:43:59

        So I'd like to, I'd certainly like to be aware of that.

    20. KNKari Nadeau1:44:01

        Yeah. Okay.

    21. PAPeter Attia1:44:02

        Um, but anyway, thank you very much for most of all your work. Um, I've seen firsthand the impact it has had on people's lives, and I know that there are probably a lot of people who are hearing about this for the very first time today. There are people who are listening to us or watching us who know somebody who suffers from a devastating anaphylactic reaction, who probably at this point in time are completely unaware that such a therapy exists. I guess my final point is, what would you suggest for those people? Someone listening or hearing this who is being blown away by what you're telling them, where can they either find a clinical trial or find, um, a, a non-clinical trial provider who's able to, to walk them down this pathway?

    22. KNKari Nadeau1:44:43

        Absolutely. Well, first of all, thank you, Peter. Thank you for your excellent questions as always. I'm really excited to be on the show, and, and thank you for your curiosity and your, and your care on this podcast. For people that are learning about this newly, um, what's wonderful is you can get on your computer, do a search on clinicaltrials.gov, look under the category of food allergy, and you can find out what clinical trial nearby you is actually ongoing for food allergy therapy. And there's a lot more than there were just five years ago, so that's good. There's like 17 companies in this space now. I'm really excited about the future. There is a lot of hope and promise. Within that hope and promise, there are more clinics around the country as well that are specializing in food allergy. I gave you one example of Latitude, but there are others as well. And so with that in mind, I would go to your healthcare provider, ask them questions. If you feel like they don't have time or they haven't really answered the questions in the way that you learned about today, go online and find out those clinics that specialize in food allergy therapy. And again, not everyone fits with everyone, so t- give it a test, see if you like that structure, and then you can try. And I hope the best, because that possibility is there, that reality is there, and I hope everyone tries to undergo therapy.

    23. PAPeter Attia1:45:57

        Kari, thank you so much. This was absolutely fascinating.

    24. KNKari Nadeau1:46:00

        Thank you. Thanks for your great questions. [upbeat music]

Episode duration: 1:46:12